DESCRIPTION: The proposed research program will investigate mechanisms of neoplastic transformation of neuroectodermal cell types in the peripheral nervous system. A unique animal system, damselfish neurofibromatosis (DNF), will be used to address basic questions in the pathogenesis of tumors such as neurofibromas and neurofibrosarcomas. DNF is caused by a transmissible, sub-cellular agent and appears to be the only example of a transmissible tumor involving any neuroectodermally derived cell type. This research will emphasiz characterization of the etiologic agent of DNF and the use of this agent as a tool to understand pathogenesis in this disease through three closely related aims: (1) The hypothesis will be tested that a novel group of extrachromosomal DNAs found in DNF tumors is the etiologic agent of DNA, (2) This agent, termed DNFX, will be characterized to determine the sequence of the DNA genome and RN transcripts and to examine the relationship of DNFX to determine the sequence of the DNA genome and RNA transcripts and to examine the relationship of DNFX to defined families of viruses and virus-like agents. (3) Proteins encoded by DNFX will be identified and antibodies developed to determine the distribution of DNFX proteins in tissues and to identify cellular proteins that may be boun by DNFX proteins.